(NEUROIMAGINGANDNEUROCIRCUITRY(NNC):COREE) PROJECT SUMMARY Description: The Neuroimaging and Neurocircuitry Core (NNC) enables the study of changes in brain circuitry which occur in people with IDD. The Core supports research in both patients and animal models by providing users the following state-of-the-art technologies: (a) Magnetoencephalographic (MEG) recordings of brain activity; (b) Magnetic resonance imaging (MRI) studies of brain structure and function; (c) Multiphoton, confocal, and epifluorescence microscopic imaging studies of the dynamics of neuronal circuit function; (d) Patch clamp recording studies in neurons; and (e) Electroencephalographic (EEG) and other in vivo recordings. Analyses are performed in affected human patients with IDD, in Preclinical animal models of IDD, and in vitro (stem cells and tissue culture). Core Directors provide users with access to a wide set of otherwise inaccessible neuronal circuit assessment techniques, as well as expert consultation regarding experimental design and analysis. In all core functions, emphasis is placed upon quality control. In addition to assuring that all studies are competently conducted and appropriately analyzed, the Core Directors assist users to design studies that are properly controlled, adequately powered, and, when feasible, conducted in a blinded fashion. Relevance to IDDRC Mission: The overarching theme of this IDDRC is ?Genes, Brain & Behavior? (see Overview). This Core focuses on each of these overlapping domains. Genetic alterations underlie many IDDs, and result in aberrant protein expression, which alters basic brain function. This in turn generates the behavioral anomalies which constitute IDD. The study of patients and animal models brings the genetic components into sharp focus, and the NNC facilitates examination into how these genetic changes alter brain function and, subsequently, whether such changes are correlated to behavior. Thus, the goal of the Core is to quantify the changes in function of neuronal circuits which result from genetic mutation and variation. Elucidating the changes in dynamic function of neuronal circuitry responsible for the generation of the pathologic behaviors collectively termed the IDD is critical in translational efforts to develop better therapies to treat and cure brain pathologies underlying the IDDs and other related CNS disorders such as autism, epilepsy, and cerebral palsy. Eligibility: These services are available both to approved users of the IDDRC at CHOP/UPenn and to users at other Centers in the Network.